The Tissue Core will collect tissue from subjects in Project 1 and distribute it to Projects 2 and 3. Specifically: Brains of Project 1 rats (Dr. Roberts) that self-administer cocaine under the DT4 schedule, with and without exposure to candidate medications, will be hemisected and distributed to Project 2 for analysis of immediate early gene expression (Dr. Porrino) and tissue neurotransmitter content (Dr. Jones). Brains of Project 1 rats (Dr. Roberts) that self-administer cocaine under the progressive-ratio schedule, with and without exposure to candidate medications, will be hemisected and distributed to Project 3 for analysis of receptor binding and G-protein receptor function (Dr. Childers) and signal transduction systems (Dr. Howlett). Brains of monkeys that self-administer cocaine under the progressive-ratio schedule in Project 1 (Dr. Nader) will be hemisected and distributed as follows: one hemisphere will be distributed to Project 2 for in vitro receptor autoradiography (Dr. Porrino) and tissue neurotransmitter content (Dr. Jones). the other hemisphere will be distributed to Project 3 for identification of candidate genes and proteins via laser capture dissection (Dr. Hemby). In later years of the Center, these experiments will include synaptosomal preparations. In addition to distributing tissue from Project 1, the Tissue Core will treat separate groups of rats with drugs found to demonstrate efficacy in reducing self-administration rats in Project 1. Brains from these rats will be distributed to Project 3 for assessment of G-protein receptor function (Dr. Childers) and changes in signal transduction systems (Dr. Howlett). In addition to brain tissue, cerebrospinal fluid and venous blood will be periodically collected from nonhuman primates in Project 1 and stored for future use by investigators within and outside the Center. Several additional tissues will be collected at necropsy, including the pituitary gland, heart, myocardium, pancreatic tail, Kver lobe and adrenal glands. This list can be expanded based on future research questions and collaborations within and outside the Center.